RESUMEN
1. The effect of changes in fatty acid beta-oxidation activity on triglyceride and cholesteryl ester synthesis were studied in cultured smooth muscle cells (SMC) and in a macrophage cell line IC-21 in the presence of oleic acid (100 microM). 2. Etomoxir, an inhibitor of carnitine palmitoyltransferase I, stimulated the incorporation of [2-3H]glycerol into triglycerides in SMC and in macrophages 6.2- and 8.2-fold, respectively, and the incorporation of [4-14C]cholesterol into cholesteryl esters in macrophages 3.5-fold. 3. L-Carnitine, a cofactor of fatty acid beta-oxidation, decreased the incorporation of [2-3H]glycerol into triglycerides in smooth muscle cells by 69% and the incorporation of [4-14C]cholesterol into cholesteryl esters by 52%. L-Carnitine had no effect on the macrophages.
Asunto(s)
Ácidos Grasos/metabolismo , Metabolismo de los Lípidos , Macrófagos/metabolismo , Músculo Liso Vascular/metabolismo , Animales , Carnitina/farmacología , Carnitina O-Palmitoiltransferasa/antagonistas & inhibidores , Línea Celular , Células Cultivadas , Colesterol/metabolismo , Ésteres del Colesterol/biosíntesis , Vasos Coronarios , Compuestos Epoxi/farmacología , Glicerol/metabolismo , Macrófagos/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Oxidación-Reducción , Porcinos , Triglicéridos/biosíntesisRESUMEN
In cultured pig coronary smooth muscle cells phorbol 12-myristate 13-acetate (PMA) stimulated the conversion of [4-14C]cholesterol into cholesteryl esters and the incorporation of [2-3H]glycerol into triglycerides 6.4- and 4.5-fold, respectively. The maximal effects occurred after 3 h of treatment and there was a return to basal values after 72 h. In the presence of 400 microM oleic acid, PMA stimulated the conversion of [4-14C]cholesterol into cholesteryl esters and that of [2-3H]glycerol into triglycerides 5.3- and 2.3-fold, respectively. The stimulatory effects were more sustained (still significant after 72 h) and their maxima were delayed (peaks after 24 h). PMA was also found to increase 2-fold the amount of triglyceride that accumulated in the cells in the presence of oleic acid after 24 h. In macrophages IC-21, the effects of PMA were observed only in the presence of oleic acid. They consisted of a 1.9-fold stimulation in the conversion of [4-14C]cholesterol into cholesteryl esters after 72 h and of a 1.7-fold stimulation in the incorporation of [2-3H]glycerol into triglycerides after 24 h. PMA also increased the amount of triglyceride that accumulated in the cells 1.9-fold after 72 h. It is concluded that PMA, and possibly growth factors, may promote lipid storage in smooth muscle cells and that fatty acids favor long lasting effects of PMA in smooth muscle cells and are necessary for any effect of PMA in macrophages.